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Dendrodoine A, grossularines-1 and -2, metabolites isolated from the tunicate Dendrodoa grossularia, have exhibited a cytotoxic activity on L1210 leukemia cells in culture. The inhibition of DNA synthesis induced by grossularines and the plane structure of the alpha-carboline common moiety were in favor of an intercalative process for their mechanism of action. In fact, the results of viscometry, fluorescence quenching and DNA melting experiments clearly indicated the intercalative properties of grossularine-2 explained by its quasi-planar structure and the non-intercalative DNA binding of grossularine-1 explained by the presence of a bulky indole chain at the 2-position of the alpha-carboline ring. |
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